title: The effect of a platelet cholesterol modulation on the acetylsalicylic acid-mediated blood platelet inhibition in hypercholesterolemic patients.
abstract: Aspirin (acetylsalicylic acid, ASA) is widely used in the prevention of cardiovascular disease, but its beneficial effects may be restrained in some individuals, where the reduced ability of ASA to protect against arterial thrombotic events is observed. We analyzed the influence of the treatment with atorvastatin (10mg/day) on the platelet sensitivity to ASA monitored under in vitro conditions in hypercholesterolemic patients. The associations between plasma or platelet cholesterol parameters and the ASA-mediated inhibition of platelet reactivity or the extent of platelet protein acetylation by ASA were estimated in the patients treated with atorvastatin for 1, 3, or 6 months. Out of 27 patients, in 17 individuals platelets appeared significantly more sensitive to 50 μM ASA in arachidonic acid- or collagen-induced whole blood aggregation following 1 month atorvastatin therapy (inhibition by 60.9 ± 5.6% vs. 48.8 ± 5.4%, P<0.05 for 0.5mM arachidonic acid, 40.8 ± 2.9% vs. 27.0 ± 4.1%, P<0.05 for 1 μg/ml collagen), and this effect lasted for 3 and 6 months, remaining in a weak, although significant, relation to the reduction of platelet cholesterol content (R(S)=-0.277, P<0.002 for arachidonic acid, R(S)=-0.197, P<0.02 for collagen). It was, however, not dependent upon either antiplatelet action or plasma lipid-lowering activity of atorvastatin. In addition, in about 50% of patients, we noticed that ASA (50 μM) significantly and time-dependently diminished thromboxane B(2) concentration in atorvastatin-treated patients. The ASA-induced acetylation of platelet proteins significantly increased in the course of atorvastatin therapy and was associated with reduced platelet cholesterol (R(S)=-0.598, P<0.0001). In conclusion, statin therapy may improve platelet sensitivity to ASA in some hypercholesterolemic patients. This effect may extend beyond the action of atorvastatin as merely a lipid-lowering agent. The mechanisms of resistance of some patients to such a combined ASA-statin treatment remain to be elucidated.
authors.affiliation: Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, Poland.
authors.forename: Boguslawa
authors.initials: B
authors.lastname: Luzak
authors.forename: Magdalena
authors.initials: M
authors.lastname: Boncler
authors.forename: Joanna
authors.initials: J
authors.lastname: Rywaniak
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Wilk
authors.forename: Lidia
authors.initials: L
authors.lastname: Stanczyk
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Czyz
authors.forename: Jacek
authors.initials: J
authors.lastname: Rysz
authors.forename: Cezary
authors.initials: C
authors.lastname: Watala
mesh_terms: D000107:Acetylation / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology*; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D004347:Drug Interactions; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D001798:Blood Proteins; D006538:Heptanoic Acids; D008077:Lipoproteins, LDL; D011758:Pyrroles; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D000069059:Atorvastatin; D001241:Aspirin